Why disease ecology needs life-history theory: a host perspective

When facing an emerging infectious disease of conservation concern, we often have little information on the nature of the host-parasite interaction to inform management decisions. However, it is becoming increasingly clear that the life-history strategies of host species can be predictive of individual- and population-level responses to infectious disease, even without detailed knowledge on the specifics of the host-parasite interaction. Here, we argue that a deeper integration of life-history theory into disease ecology is timely and necessary to improve our capacity to understand, predict and mitigate the impact of endemic and emerging infectious diseases in wild populations. Using wild vertebrates as an example, we show that host life-history characteristics influence host responses to parasitism at different levels of organisation, from individuals to communities. We also highlight knowledge gaps and future directions for the study of life-history and host responses to parasitism. We conclude by illustrating how this theoretical insight can inform the monitoring and control of infectious diseases in wildlife

Fluctuating selection models and Mcdonald-Kreitman type analyses

It is likely that the strength of selection acting upon a mutation varies through time due to changes in the environment. However, most population genetic theory assumes that the strength of selection remains constant. Here we investigate the consequences of fluctuating selection pressures on the quantification of adaptive evolution using McDonald-Kreitman (MK) style approaches. In agreement with previous work, we show that fluctuating selection can generate evidence of adaptive evolution even when the expected strength of selection on a mutation is zero. However, we also find that the mutations, which contribute to both polymorphism and divergence tend, on average, to be positively selected during their lifetime, under fluctuating selection models. This is because mutations that fluctuate, by chance, to positive selected values, tend to reach higher frequencies in the population than those that fluctuate towards negative values. Hence the evidence of positive adaptive evolution detected under a fluctuating selection model by MK type approaches is genuine since fixed mutations tend to be advantageous on average during their lifetime. Never-the-less we show that methods tend to underestimate the rate of adaptive evolution when selection fluctuates

The novel mu-opioid antagonist, GSK1521498, reduces ethanol consumption in C57BL/6J mice.

RATIONALE Using the drinking-in-the-dark (DID) model, we compared the effects of a novel mu-opioid receptor antagonist, GSK1521498, with naltrexone, a licensed treatment of alcohol dependence, on ethanol consumption in mice. OBJECTIVE We test the ability of GSK1521498 to reduce alcohol consumption and compare its intrinsic efficacy to that of naltrexone by comparing the two drugs at doses matched for equivalent receptor occupancy. METHODS Thirty-six C57BL/6J mice were tested in a DID procedure. In 2-day cycles, animals experienced one baseline, injection-free session, and one test session when they received two injections, one of test drug and one placebo. All animals received GSK1521498 (0, 0.1, 1 and 3 mg/kg, i.p., 30 min pre-treatment) and naltrexone (0, 0.1, 1 and 3 mg/kg, s.c. 10 min pre-treatment) in a cross-over design. Receptor occupancies following the same doses were determined ex vivo in separate groups by autoradiography, using [3H]DAMGO. Binding in the region of interest was measured integrally by computer-assisted microdensitometry and corrected for non-specific binding. RESULTS Both GSK1521498 and naltrexone dose-dependently decreased ethanol consumption. When drug doses were matched for 70-75 % receptor occupancy, GSK1521498 3 mg/kg, i.p., caused a 2.5-fold greater reduction in alcohol consumption than naltrexone 0.1 mg/kg, s.c. Both GSK1521498 and naltrexone significantly reduced sucrose consumption at a dose of 1 mg/kg but not 0.1 mg/kg. In a test of conditioned taste aversion, GSK1521498 (3 mg/kg) reduced sucrose consumption 24 h following exposure to a conditioning injection. CONCLUSIONS Both opioid receptor antagonists reduced alcohol consumption but GK1521498 has higher intrinsic efficacy than naltrexone

Local Optical Probe of Motion and Stress in a multilayer graphene NEMS

Nanoelectromechanical systems (NEMSs) are emerging nanoscale elements at the crossroads between mechanics, optics and electronics, with significant potential for actuation and sensing applications. The reduction of dimensions compared to their micronic counterparts brings new effects including sensitivity to very low mass, resonant frequencies in the radiofrequency range, mechanical non-linearities and observation of quantum mechanical effects. An important issue of NEMS is the understanding of fundamental physical properties conditioning dissipation mechanisms, known to limit mechanical quality factors and to induce aging due to material degradation. There is a need for detection methods tailored for these systems which allow probing motion and stress at the nanometer scale. Here, we show a non-invasive local optical probe for the quantitative measurement of motion and stress within a multilayer graphene NEMS provided by a combination of Fizeau interferences, Raman spectroscopy and electrostatically actuated mirror. Interferometry provides a calibrated measurement of the motion, resulting from an actuation ranging from a quasi-static load up to the mechanical resonance while Raman spectroscopy allows a purely spectral detection of mechanical resonance at the nanoscale. Such spectroscopic detection reveals the coupling between a strained nano-resonator and the energy of an inelastically scattered photon, and thus offers a new approach for optomechanics

Tumor taxonomy for the developmental lineage classification of neoplasms

BACKGROUND: The new "Developmental lineage classification of neoplasms" was described in a prior publication. The classification is simple (the entire hierarchy is described with just 39 classifiers), comprehensive (providing a place for every tumor of man), and consistent with recent attempts to characterize tumors by cytogenetic and molecular features. A taxonomy is a list of the instances that populate a classification. The taxonomy of neoplasia attempts to list every known term for every known tumor of man. METHODS: The taxonomy provides each concept with a unique code and groups synonymous terms under the same concept. A Perl script validated successive drafts of the taxonomy ensuring that: 1) each term occurs only once in the taxonomy; 2) each term occurs in only one tumor class; 3) each concept code occurs in one and only one hierarchical position in the classification; and 4) the file containing the classification and taxonomy is a well-formed XML (eXtensible Markup Language) document. RESULTS: The taxonomy currently contains 122,632 different terms encompassing 5,376 neoplasm concepts. Each concept has, on average, 23 synonyms. The taxonomy populates "The developmental lineage classification of neoplasms," and is available as an XML file, currently 9+ Megabytes in length. A representation of the classification/taxonomy listing each term followed by its code, followed by its full ancestry, is available as a flat-file, 19+ Megabytes in length. The taxonomy is the largest nomenclature of neoplasms, with more than twice the number of neoplasm names found in other medical nomenclatures, including the 2004 version of the Unified Medical Language System, the Systematized Nomenclature of Medicine Clinical Terminology, the National Cancer Institute's Thesaurus, and the International Classification of Diseases Oncolology version. CONCLUSIONS: This manuscript describes a comprehensive taxonomy of neoplasia that collects synonymous terms under a unique code number and assigns each tumor to a single class within the tumor hierarchy. The entire classification and taxonomy are available as open access files (in XML and flat-file formats) with this article

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

On dynamic network entropy in cancer

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte

Substantial Seasonal Contribution of Observed Biogenic Sulfate Particles to Cloud Condensation Nuclei

Biogenic sources contribute to cloud condensation nuclei (CCN) in the clean marine atmosphere, but few measurements exist to constrain climate model simulations of their importance. The chemical composition of individual atmospheric aerosol particles showed two types of sulfate-containing particles in clean marine air masses in addition to mass-based Estimated Salt particles. Both types of sulfate particles lack combustion tracers and correlate, for some conditions, to atmospheric or seawater dimethyl sulfide (DMS) concentrations, which means their source was largely biogenic. The first type is identified as New Sulfate because their large sulfate mass fraction (63% sulfate) and association with entrainment conditions means they could have formed by nucleation in the free troposphere. The second type is Added Sulfate particles (38% sulfate), because they are preexisting particles onto which additional sulfate condensed. New Sulfate particles accounted for 31% (7 cm−3) and 33% (36 cm−3) CCN at 0.1% supersaturation in late-autumn and late-spring, respectively, whereas sea spray provided 55% (13 cm−3) in late-autumn but only 4% (4 cm−3) in late-spring. Our results show a clear seasonal difference in the marine CCN budget, which illustrates how important phytoplankton-produced DMS emissions are for CCN in the North Atlantic

Disorder Effects on Exciton-Polariton Condensates

The impact of a random disorder potential on the dynamical properties of Bose Einstein condensates is a very wide research field. In microcavities, these studies are even more crucial than in the condensates of cold atoms, since random disorder is naturally present in the semiconductor structures. In this chapter, we consider a stable condensate, defined by a chemical potential, propagating in a random disorder potential, like a liquid flowing through a capillary. We analyze the interplay between the kinetic energy, the localization energy, and the interaction between particles in 1D and 2D polariton condensates. The finite life time of polaritons is taken into account as well. In the first part, we remind the results of [G. Malpuech et al. Phys. Rev. Lett. 98, 206402 (2007).] where we considered the case of a static condensate. In that case, the condensate forms either a glassy insulating phase at low polariton density (strong localization), or a superfluid phase above the percolation threshold. We also show the calculation of the first order spatial coherence of the condensate versus the condensate density. In the second part, we consider the case of a propagating non-interacting condensate which is always localized because of Anderson localization. The localization length is calculated in the Born approximation. The impact of the finite polariton life time is taken into account as well. In the last section we consider the case of a propagating interacting condensate where the three regimes of strong localization, Anderson localization, and superfluid behavior are accessible. The localization length is calculated versus the system parameters. The localization length is strongly modified with respect to the non-interacting case. It is infinite in the superfluid regime whereas it is strongly reduced if the fluid flows with a supersonic velocity.Comment: chapter for a book "Exciton Polaritons in Microcavities: New Frontiers" by Springer (2012), the original publication is available at http://www.springerlink.co

Effects of affective picture viewing on postural control

<p>Abstract</p> <p>Background</p> <p>Emotion theory holds that unpleasant events prime withdrawal actions, whereas pleasant events prime approach actions. Recent studies have suggested that passive viewing of emotion eliciting images results in postural adjustments, which become manifest as changes in body center of pressure (COP) trajectories. From those studies it appears that posture is modulated most when viewing pictures with negative valence. The present experiment was conducted to test the hypothesis that pictures with negative valence have a greater impact on postural control than neutral or positive ones. Thirty-four healthy subjects passively viewed a series of emotion eliciting images, while standing either in a bipedal or unipedal stance on a force plate. The images were adopted from the International Affective Picture System (IAPS). We analysed mean and variability of the COP and the length of the associated sway path as a function of emotion.</p> <p>Results</p> <p>The mean position of the COP was unaffected by emotion, but unipedal stance resulted in overall greater body sway than bipedal stance. We found a modest effect of emotion on COP: viewing pictures of mutilation resulted in a smaller sway path, but only in unipedal stance. We obtained valence and arousal ratings of the images with an independent sample of viewers. These subjects rated the unpleasant images as significantly less pleasant than neutral images, and the pleasant images as significantly more pleasant than neutral images. However, the subjects rated the images as overall less pleasant and less arousing than viewers in a closely comparable American study, pointing to unknown differences in viewer characteristics.</p> <p>Conclusion</p> <p>Overall, viewing emotion eliciting images had little effect on body sway. Our finding of a reduction in sway path length when viewing pictures of mutilation was indicative of a freezing strategy, i.e. fear bradycardia. The results are consistent with current knowledge about the neuroanatomical organization of the emotion system and the neural control of behavior.</p